Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease. In the U.S., PDAC is the fourth leading cause of cancer death, with average survival of less than 1 year from diagnosis. To date, surgery has been the only curative treatment; however, only 20% of patients are candidates for surgical resection. Moreover, subsets of patients who initially appear to have resectable tumors are subsequently found to have locally advanced disease, in which a margin-negative resection is not feasible. Unfortunately, no effective treatments for locally invasive and metastatic PDAC are known at this time.
Optionally, prodrugs can be used in the treatment of cancer. Prodrugs are compounds that are administered in an inactive or less than fully active form. These compounds are then processed or converted to an active therapeutic agent through normal metabolic processes. Prodrugs are sometimes referred to as precursors as they serve as a type of precursor to the intended active therapeutic agent.
Currently, photodynamic therapy (PDT) is a widely accepted treatment modality for many cancerous and precancerous lesions, including those in bladder, brain, ovary, and skin. It is a minimally invasive treatment that damages the target cells by imparting cytotoxicity through generation of reactive oxygen species. The individual PDT components, including photosensitizer (PS), light, and oxygen, are nontoxic. However, upon illumination of the light-sensitive PS in the presence of oxygen, highly reactive singlet oxygen (1O2) species are generated within the tumor tissue, causing severe damage to all cells in the vicinity of the treated area. Although the intravenously administrated photosensitizers accumulate in the intended tumor tissue, they also undergo non-specific distribution to non-target tissues, resulting in unavoidable damage to the normal cells. Therefore, the patients must avoid light for a long period until the concentration of the sensitizer decreases to an acceptable level.